TFPIb, a Second Product from the Mouse Tissue Factor Pathway Inhibitor (TFPI) Gene
Jen-Yea Chang, Dougald M. Monroe, Julie A. Oliver, Harold R. Roberts
From the Center for Thrombosis and Hemostasis, University of North Carolina, Chapel Hill, USA
Summary Tissue factor pathway inhibitor (TFPI) contains three Kunitzdomains separated by two connecting regions. We have cloned anothernaturally occurring TFPI gene product from a mouse lung cDNAlibrary which we have called TFPIb. TFPIb is derived from alternativesplicing of the TFPI gene. Analysis of the cDNA shows that mouseTFPIb protein is identical to TFPI from the N’-terminus through thesecond connecting region. However, mouse TFPIb possesses neither athird Kunitz domain nor an Arg, Lys-rich C’-terminus but instead has acompletely different C’-terminal (b-domain) sequence which is nothomologous to any known protein. Northern blot analyses show thatthe tissues for mouse TFPIb synthesis are heart and lung; in contrast,TFPI appears in Northern blots of heart and spleen. Both TFPIb andTFPI messages first appear in 7-day-old mouse embryos, but only theTFPI mRNA persists until 17 days. Purified recombinant TFPIb showsan apparent molecular weight of 38 kDa. Kinetic studies indicate thatmouse TFPIb is a slow-binding enzyme inhibitor for human factor Xa.In addition, heparin does not enhance the inhibition of factor Xa bymouse TFPIb although it does accelerate factor Xa inhibition by TFPI.